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t-TG IgG

The t-TG IgG test is a chemiluminescent immunoassay (CLIA), for use on IDS automated analyzers. It is used for the quantitative determination of the specific IgG antibodies directed against tissue transglutaminase in human samples of serum or plasma (EDTA and Heparin).

Celiac disease (CD) or gluten intolerance is an autoimmune disorder that occurs in genetically predisposed subjects and is triggered by a diet rich in cereals such as wheat, barley, and rye.1

Genetic predisposition to CD is linked principally to several HLA system genes; in particular to genotypes DQ2 and DQ8, which are present in 95-98% of celiac patients and occur in 20-30% of the general population.2,3 The prevalence of CD in the Caucasian population is 1:100 ca; that is, one person in 30 who carries the alleles coded by the HLA DQ2/DQ8 genes develops CD.4,5

Gliadin is a gluten protein that can trigger the autoimmune process; contact between the gliadin peptides and the cells of the immune system of the intestinal submucosa can occur following alteration of intestinal permeability induced by zonulin secreted by enterocytes. Gliadin is an excellent substrate for the tissue transglutaminase ( t-TG ) enzyme; deamidation and transamidation of the gliadin peptides by t-TG modify the overall charge of the molecule, permitting it to bind with the HLA DQ2-DQ8 antigens expressed by the cells presenting the antigen to form a HLA DQ2-DQ8 / deamidated peptide / t-TG complex. This complex is recognized by the CD46 T lymphocytes, which trigger the immune process with activation of the effector T cells, production of cytokines, proliferation of B lymphocytes, and synthesis of anti-t-TG antibodies7 and antibodies against gliadin peptides.8,9 The net result is an inflammatory process presenting various histologies that can escalate to (reversible) lesions of the intestinal mucosa such as villous atrophy.

Serological testing plays a crucial role in diagnosis of CD and in monitoring compliance to treatment characterized by a gluten-free dietary regime.

As recommended by international guidelines, the first-line approach to diagnosis of CD is testing for anti-t-TG IgA autoantibodies associated with the test for total IgA; this approach is suggested because the risk that subjects with an absolute IgA deficiency (IgA ≤ 5 mg/dl)10 will develop CD is 10 times greater than in the normal population.11

The high sensitivity and specificity of the anti-transglutaminase IgA autoantibody assays, respectively 96-98% and 93-95%,12 associated with the objectivity and full automation offered by the test, have meant that in recent years anti-t-TG IgA testing has superseded older serological tests for CD.13 Testing for anti-endomysial IgA antibodies (EMA) nevertheless plays an important role in confirming positivity in all sera that test anti-t-TG IgA positive, due to the high specificity (99-100%) of the EMAs, even though significant interpretative issues remain. In selective IgA deficiencies, the anti-t-TG IgG test must be associated with testing for IgG antibodies against deamidated gliadin peptides (a-DGP).

It has recently been demonstrated that celiac subjects synthesize specific antibodies against certain deamidated gliadin peptides. The anti-DGP antibodies are highly specific markers for identifying gluten-intolerant subjects, differently from the anti-gliadin antibodies in total, which are also found in healthy subjects or in subjects affected by other enteric disorders and are therefore less specific.14

The anti-DGP IgA antibody tests show a sensitivity of 86-95% and a specificity of 91-95%, while the IgG antibody tests show 84-98% sensitivity and 95-98% specificity; these performance figures suggest use in pediatric subjects,15 in whom synthesis of the latter antibodies would seem to precede synthesis of anti-transglutaminase IgA antibodies. Use of the test for anti-DGP IgA and IgG antibodies is also recommended in all subjects, regardless of age, showing symptoms suggestive of CD and in whom the t-TG or EMA autoantibodies are absent or present only at low titers.16

Celiac patients on gluten-free diets show a progressive reduction of anti-t-TG and anti-gliadin antibodies. The IgG antibody titer decreases more slowly than does the IgA antibody count.